KR101405859B1 - Dental implant coated with a mixed solution of chemical buffering agent and organic amphoteric substance and a prepareation process thereof - Google Patents

Abstract

The present invention relates to a bioactive hydrophilic dental implant which coats a preprocessed surface with a mixed solution including an organic chemical buffering agent and/or inorganic chemical buffering agent and organic amphoteric substance to remove pollutants as a titanium or a titanium alloy dental implant. The implant biocompatibility, bodily fluids and blood compatibility, and initial osseointegration can be improved by preventing the implant surface from the hydrophobic modification due to the organic pollutants before implanting the dental implant to an alveolar bone and prevents the degradation of bioactivity due to the surface hydrophobic modification by coating the surface of the organic-pollutants-removed dental implant with the mixed solution including the chemical buffering agent and organic substances (BES, HEPES, MOPS, PIPES and TES). Also, the osseointegration time can be reduced not only by increasing the initial osseointegration after the implant operation since the coated layer is bioactive, biocompatible, bodily fluids and blood compatible; but also effectively prevent the absorption of the pollutants in the air to the surface. The dental implant surface can be maintained as hydrophilic for at least 3 years using the mixed solution of the chemical buffering agent and organic amphoteric substances as a surface coating solution.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dental implant coated with a mixed solution of a pH buffer material and an organic amphoteric substance having a sulfone group and a preparation method thereof,

The present invention improves existing surface treatment methods of Resorbable Blasted Media blasting (RBM) and Sandblast Large Grit Acid Etch (SLA) in which an implant surface of a titanium or titanium alloy material having a rough surface is contaminated with organic pollutants, A dental implant coated with a mixed solution containing an organic or inorganic pH buffering agent (pH buffering substance) and an organic amphipatic compound and a method for producing the same are provided to maintain superfluidity of the surface of the implant. Through this, bioactivity of the surface of RBM or SLA is improved, the fluids and blood affinity are improved for a long period of time of about 3 years or more, and ultimately, the bioactivity with excellent biocompatibility, osteogenesis effect and short- Enhanced dental metal implants may be provided.

Surface treatment of dental implants has been recognized as an important factor in osseointegration, and is a smooth surface treatment method by lathe machining with implant surface treatment method. These surface treatments have improved the biocompatibility and tissue stability of the bone, and have been used for a long time in implant surgery. However, efforts have been made to improve the surface properties to improve the success rate in low-density bone, and Predecki et al. Reported that implants with irregular surfaces can have fast bone growth and excellent mechanical adhesion. In addition, Buser et al. Suggested that implants with irregular and rough surfaces in animal studies have higher bone contact rates than implants with smooth surfaces.

The developmental stages of the implant surface can be divided into first generation implants with smooth surfaces, second generation implants with rough surfaces, and third generation implants with chemically modified coating surfaces. Examples of the second-generation implants include Resorbable Blasted Media blasting (RBM) and Titanium Plasma Spray (TPS), which increase the roughness of implants using a blasting technique as an absorbent medium. In addition, the surface of the third generation implant with a hydroxyapatite (HA) coating surface has an increased surface area due to the influence of the particles and coating sprayed on the surface, thereby increasing the bone interface of the implant interface and activating the cell reaction on the rough surface .

However, in the case of surface treatment methods such as RBM and SLA, which are currently widely used, when the product is exposed to the air after the surface treatment process, the oxide layer grows on the surface of the product and the adsorption of various contaminants such as hydrocarbons proceeds , There is a problem that it is hydrophobic while changing to a chemically stable state. This hydrophobic surface has a disadvantage in that it impedes the overall treatment or implantation process that fuses with the bone after implantation because of low wettability to body fluids and blood, and prolongs the stability period of the implant.

According to US Pat. No. 6,702,855 which is a conventional technique, there is proposed a method of chemically etching using inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid or the like in order to improve the hydrophobicity of the titanium implant surface. (Radio-frequency glow discharge (RFGD), O _2, etc.), light irradiation (ultraviolet ray, ultraviolet ray-ozone, etc.) method can be considered as a method of imparting hydrophilicity. Although it is possible to super-hydrophilize the titanium surface for a short period of time using this known conventional technique, there still remains a problem in maintaining such superhydrophilicity for a long period of time, and Suzuki et al. Have reported that 4- (2-Hydroxylethyl) 1-piperazineethanesulfonic acid is used to hydrophilize the surface of titanium, but it is only about 3 months to maintain hydrophilicity.

Ultrasonic hydration of the surface of the dental implant is a very important factor in the initial bone formation ability and biocompatibility of the oral cells, and the pH of the surface of the implant also plays a very important role in hydrophilic maintenance and surface characteristics. Particularly, extracellular microenvironment such as changes in blood flow, nutrients, and potential of hydrogen (pH) influences cell activity, morphological changes and functions in various cells constituting the alveolar bone including osteoblasts and osteoclasts of implant implants (Ramp WK. Lenz LG & Kaysinger KK).

In other words, the change in pH due to the biomedical process, fracture, pathological environment including metabolic diseases, or implantation of biomaterial including implants changes the cellular metabolism related to the osteoblast and osteoclast proliferation and osteoclast proliferation ability And this extracellular pH change in vivo is strictly controlled to maintain bioactive acid base equilibrium. However, this equilibrium has been known to cause acidosis or alkalosis due to collapse of acid base equilibrium for several reasons. Typically, the bone is removed or the implant fixture is placed for planarization of the alveolar bone during implantation. In the pathological environment such as surgical treatment or fracture, such as drilling (surgical act of putting a hole with a similar shape so that an implant fixture can be placed on the alveolar bone), the pH of the bone marrow microenvironment rapidly drops It is known that the pH of approximately 4 to 5 is maintained for 1 to 2 weeks (Hench LL and Ethridge EC).

In the study of bone metabolism according to pH change, when pH was lowered and acidification occurred, osteoblast activity was decreased, collagen accumulation of extracellular matrix (ECM) was inhibited, osteoblast And Runx2 expression by inhibiting bone mineralization (mineralization). In addition, pH-lowering activates osteoclasts by increasing the expression of the receptor activator of nuclear factor kappa-B ligand (RANKL) and parathyroid hormone receptor, and activated osteoclasts promote bone remodeling, .

On the other hand, it has been reported that when the pH is increased to alkaline, unlike acidification, osteoblast activity is increased, ALP activity and collagen synthesis are increased, and bone marrow stromal cell is differentiated into osteoblast. This may lead to a positive phenomenon that the mineralization is accelerated and the bone formation is increased in the bone environment (Arnett TR, Kohn et al., Brandao-Burch A et al.

As described above, according to the existing prior art literature on the pH of the bone microenvironment, the pH of the initial implant portion is controlled in the implant portion of the alveolar bone, so that the pH of the implant implant portion is constant from neutral to weakly alkaline This is important because it affects not only the implant-bone interface bone formation but also the implant success rate in the long term.

Therefore, in the present invention, an alkaline pH buffering material and an organic amphipatic material (in particular, a sulfone) are used in order to neutralize the initial pH of the dental implant portion and to maintain the thus appropriately controlled microenvironment so as to improve initial bone performance and biocompatibility. The use of a mixed solution containing an organic amphipathic substance having a group to prevent the surface of the implant from being re-contaminated to an organic pollutant source to change into a hydrophobic state, to improve the implant biocompatibility, body fluid, blood affinity and initial osseointegration performance, The present invention provides a dental implant having a shortened period and a method of manufacturing the same.

U.S. Patent No. 6,702,855

 Suzuki et al., Biomaterials, 31, 4818-4828 (2010).  Ramp WK. Lenz LG, Kaysinger KK. "Medioum pH modulates matrix, mineral and energy metabolism in cultured chick bones and osteoblast-like cells." Bone Miner., 24, 59-73 (1994).  &Quot; Biomaterials: an interfacial approach, "Hench LL and Ethridge EC, Academic Press (1982).  Arnett TR. "Extracellular pH regulates bone cell function." J. Nutr., 138, 415S-418S (2008).  Kohn DN, Sarmadi M, Helman JI, Krebsbach PH. "Effects of pH on human bone marrow stromal cells in vitro: implications for tissue engineering of bone." J. Biomedical Mater. Res., 60, 292-299 (2002).  Brandao-Burcha, Utting JC, Orriss IR, Arnett TR. "Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization." Calcif. Tissue Int., 77, 167-174 (2005).

This invention uniformly coats a mixed solution containing a chemical buffering agent on a titanium surface from which a contaminant is removed, thereby restraining the re-adsorption and stabilization of a contaminant causing surface hydrophobicity, and maintaining superhydrophilic properties of the titanium surface for a long time Thereby improving body fluids and blood affinity and ultimately achieving excellent osteogenesis and short osseointegration period after implantation.

(1) exposing a superhydrophilic titanium surface having a bioactivity by removing a contamination source adsorbed and stabilized on a titanium oxide film, (2) exposing an organic amphoteric substance having a pH buffer and a sulfonic group, To thereby form a uniform coating film

As can be seen from FIG. 1, the bioactive surface-treated metal implants manufactured by the metal implant manufacturing method according to the present invention were uniformly coated with a mixed solution containing a pH buffer material and an organic amphipatic material having a sulfone group Is formed on the surface.

A dental implant of a titanium or titanium alloy material having a rough surface comprising i) an organic pH buffering material and / or an inorganic pH buffering material and ii) an organic amphipathic material having a sulfone group on the rough surface pretreated to remove the contaminant source , The hydrophilicity of the surface of the dental implant is improved and the bone bonding performance of the dental implant is remarkably improved. Particularly, it is possible to give the effect that the improved hydrophilicity and bone-bonding performance of the dental implant is maintained without decreasing over a long period of time.

The concentration of the organic amphiphilic substance having a sulfone group in the mixed solution is preferably in the range of 0.05 to 1.68 M.

The organic amphiphilic substance having a sulfone group contained in the mixed solution may be selected from the group consisting of ACES (2- (carbamoylmethylamino) ethanesulfonic acid), BES (N, N-bis (2-hydroxyl- (2-hydroxyethyl) -1-piperazine sulfonic acid), MOPS (3- (N-morpholino) propanesulfonic acid), PIPES (1,4 -Piperazinediethanesulfonic acid) and TES (N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid).

Wherein the inorganic pH buffering substances, and acts as a base having a hydroxyl group, NaOH, KOH, Ca (OH ) 2, Ba (OH) 2, Al (OH) 3 and Sr (OH) at least any one or more of the ₂ Can be selected.

Also, the organic pH buffer material acts as a base having a pH of 8 or more and has a pKa value of 8.0 or more. Specifically, AMPD (2-amino-2-methyl-1,3-propanediol), ammonia, bicine, glycine , glycylglycine, tris, tricine, and taurine may be used.
More specifically, a dental implant of a titanium or titanium alloy material having a roughened surface of the present invention comprises i) an organic pH buffering material and / or an inorganic pH buffering material and ii) ) Sulfone group, wherein the organic pH buffer material has a pKa of at least 8.0 and at least one selected from AMPD, ammonia, bicine, glycine, glycylglycine, tris, tricine and taurine At least one selected from the group consisting of NaOH, KOH, Ca (OH) ₂ , Ba (OH) ₂ , Al (OH) ₃ and Sr (OH) ₂ having a hydroxyl group And the organic amphiphilic substance having a sulfone group contained in the mixed solution includes at least one of BES, HEPES, MOPS, and TES, and the mixed solution contains 0.05 to 1.68 M of an organic amphipatic substance And also characterized in that the pH buffer substance contained in the range of 1 ~ 10 wt% of the mixed solution.

According to another aspect of the present invention, there is provided a method for manufacturing a bioactive dental implant, comprising the steps of: preparing a dental implant of titanium or titanium alloy; A second step of roughing the surface of the dental implant; A third step of pretreating the roughened surface of the dental implant to remove contaminants; And a fourth step of forming a coating layer of a mixed solution comprising i) an organic pH buffering material and / or an inorganic pH buffering material and ii) an organic ampholytic substance having a sulfone group on the surface of the pretreated coarse dental implant , Said organic pH buffering material is at least one selected from among AMPD, ammonia, bicine, glycine, glycylglycine, tris, tricine and taurine with a pKa of 8.0 or more, said inorganic pH buffering material having a hydroxyl group, organic amphiphilic material with _{KOH, Ca (OH) 2,} Ba (OH) 2, and Al (OH) ₃ and Sr (OH) at least one selected from among _2, a group sulfone contained in the mixed solution, BES, HEPES, MOPS, and TES. In the fourth step, the mixed solution contains 0.05 to 1.68 M of organic amphipathic substance, and 1 to 10 wt% of the mixed solution Containing a pH buffer substance It characterized.

At this time, the step of removing the contamination source may be performed by one or more methods of the surface of the roughened dental implant, such as ultraviolet ray, RFGD (radio frequency glow discharge), oxygen and room temperature plasma, It may be omitted.

According to the present invention, a dental implant having an organic contamination source on its surface is pretreated through a pretreatment such as plasma or light irradiation. The dental implant is immersed in an organic amphipat (BES, HEPES, MOPS , PIPES, TES), it is possible to prevent the dental implant from being exposed to air before the dental implant is placed in the alveolar bone to re-contaminate the surface of the implant with the organic pollutant source to change into a hydrophobic state, It is possible to improve the implant biocompatibility, body fluid, blood affinity, and initial bone adhesion performance by preventing the degradation of bioactivity.

In addition, since the surface of the implant is coated with the organic pH buffering agent and the organic amphipathic substance, the surface of the implant effectively prevents the contamination of air from being adsorbed, and the coating layer uniformly formed on the surface exhibits biocompatibility, body fluid and blood affinity, The initial osseointegration performance is increased after the procedure, and the osseointegration period is finally shortened.

By adjusting the pH of the initial implant site in the alveolar bone implant site, the pH of the implant implant site can be kept constant from neutral to weakly alkaline, thereby improving the implant success rate from the long term perspective as well as implant- By using a mixed solution of a buffer substance and an organic amphoteric substance having a sulfone group as a surface coating liquid, the dental implant surface can be kept hydrophilic for at least 3 years (a period corresponding to 18 weeks of accelerated aging).

FIG. 1 schematically shows a method of manufacturing a metal implant according to the present invention in each step.
FIG. 2 shows the result of measuring the bone-interface bonding ability of the dental implant by dividing the mixed solution containing the organic amphiphilic substance (BES, HEPES, TES) having sulfone groups into the case of using the organic pH buffer material and the case of not using the organic pH buffer material It is.
FIG. 3 shows the contact angle measurement results of a titanium disk coated with a mixed solution containing a pH buffer material and an organic amphiphilic substance having a sulfone group (ACES, BES, CHES, HEPES, MOPS, PIPES, TES).
FIG. 4 shows the contact angle measurement results of a titanium disk coated with a mixed solution containing a pH buffer material and an organic amphiphilic substance having a sulfone group (ACES, BES, CHES, HEPES, MOPS, PIPES, TES).
FIG. 4 shows experimental results of cell adhesion of a titanium disk coated with a mixed solution containing a pH buffer material and an organic amphiphile having a sulfone group (ACES, BES, CHES, HEPES, MOPS, PIPES, TES).
FIG. 5 shows experimental results of blood protein adhesion of a titanium disk coated with a mixed solution containing a pH buffer substance and an organic amphiphilic substance having a sulfone group (BES, HEPES, MOPS, TES).
FIG. 6 is a graph showing blood wettability of a dental implant coated with a mixed solution containing a pH buffer material and an organic amphipathic substance having a sulfone group (BES, HEPES, MOPS, TES).
FIG. 7 is a result of measuring the bone-interface bonding ability of a dental implant coated with a mixed solution containing a pH buffer substance and an organic amphiphilic substance having sulfone groups (BES, HEPES, MOPS, PIPES, and TES)
FIG. 8 is a graph showing a result of measuring the amount of blood protein adhered to a dental implant coated with a pH buffer material and a mixed solution of BES, which is an organic amphoteric substance having a sulfone group.
FIG. 9 is a graph showing a result of measuring the amount of blood protein adhered to a dental implant coated with a pH buffer material and a sulfuric acid-containing organic amphoteric HEPES.
FIG. 10 shows the result of measurement of the amount of blood protein adhered to a dental implant coated with a mixed solution according to the concentration of TES, which is an organic amphiphilic substance having a pH buffer substance and a sulfone group.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings. Prior to this, terms and words used in the specification and claims of this invention should not be construed to be limited to ordinary or dictionary terms, It should be construed as meaning and concept consistent with the technical idea of the present invention.

It should be understood, therefore, that the drawings set forth in the specification and drawings of the invention are by way of illustration only and are not to be construed as limiting the scope of the present invention. It should be understood that various equivalents and modifications are possible.

Method of coating pH buffering material and organic amphiphile (1M)

The machined titanium implant was blasted with Al ₂ O ₃ powder having a particle size of 1 mm or less at a blast pressure of 1 to 10 atm for 1 to 60 seconds and then subjected to acid treatment using a mixed acid aqueous solution, & micro-morphology can be formed. The acid-treated titanium dental implants were ultrasonically cleaned with ethanol and distilled water for 30 minutes, respectively, and then dried.

The surfaces of the implants that had undergone the drying step were treated with plasma for 1 minute or ultraviolet rays for 5 minutes to remove contaminants adsorbed on the surface and stabilized. The surfaces of the implants were treated with an organic amphipathic (BES, HEPES, TES) 1 M aqueous solution (see Fig. 1). When the pH buffer substance was used, a mixed solution of the organic amphiphilic substance having sulfone group and the pH buffer substance was used for application of the surface of the implant. In this case as NaOH, KOH, Ca (OH) 2, Ba (OH) 2, Al (OH) 3 and Sr (OH) ₂ as one of the inorganic pH buffer material, the entire mixture solution of pH buffer substance-to 10 wt% range And at least one selected from among AMPD, ammonia, bicine, glycine, glycylglycine, tris, tricine and taurine, having a pKa value of 8.0 or more, in the range of 0.01 to 1.68 M Can be used. In addition, a mixture of the inorganic pH buffer material and the organic pH buffer material may be used together with the organic amphipathic substance having sulfone group in the mixed solution. In the following examples, NaOH, an inorganic pH buffer material, was used.

Implants coated with organic amphoteric material with or without the pH buffer material thus prepared were used in Example 2 below.

pH  Dental implants with and without buffer substances Bone interface  Bonding force measurement experiment

Bone interface strength of coated dental implants was measured by accelerated aging for solutions containing sulfo group-containing organic amphiphiles (BES, HEPES, TES) with or without pH buffering materials. After implanting the BES, HEPES, and TES coated dental implants prepared in Example 1 above under accelerated aging conditions (about 55 ° C) for 18 weeks (corresponding to a normal storage period of 3 years), the implant- The implant was placed in a micropig mandible and the removal torque was measured after 16 days of bone formation. At this time, implants that did not remove contaminants were used as a negative control, and implants that were pretreated to remove contaminants as a positive control. Bone interface strengths were compared according to presence or absence of pH buffer substances.

As shown in FIG. 2, the torsion removing ability of the positive control group was increased by about 46% as compared with the negative control group. The pretreatment was similar to that of the positive control, but the accelerated aging corresponding to 3 years of storage period was not maintained in the bioactivity and hydrophilicity of the experimental group at 18 weeks, and the torsion removing power was decreased to the negative control level. However, the BES, HEPES, The torsion removing ability was maintained at about 42%, 41%, 44% and a positive level of the positive control group, compared with the negative control group.

In addition, the BES, HEPES, and TES coating groups containing the pH buffer material added about 22%, 27%, and 24% more bone interface bonds than the BES, HEPES, and TES coating groups without the pH buffer It was confirmed that there is a remarkable synergistic effect which is improved.

pH  With buffer substances Sulfone group  Having organic Amphibian  Using a mixed solution of materials Tainium  Coating formation on the disk surface

After the contamination source was removed from the surface of the titanium disk, a coating solution was formed using a mixed solution of a pH buffer material and an organic amphipat having a sulfone group.

The machined titanium disk was blasted with Al ₂ O ₃ powder with particle size of 1 mm or less for 1 ~ 60 seconds at blast pressure of 1 ~ 10 atmospheres, and then acid- -morphology. The acid-etched dental titanium disk was ultrasonically washed with ethanol and distilled water for 30 minutes, and then dried.

A disk having been subjected to the drying process was treated with plasma for 1 minute or ultraviolet radiation for 5 minutes to remove contamination sources adsorbed and stabilized on the surface, and a pH buffer material and an organic amphipatic substance (ACES, BES, CHES, HEPES, MOPS, PIPES, TES, etc.) was uniformly applied to prepare a disk. A titanium disk coated with a mixed solution of a pH buffer material and an organic amphipat prepared by this method was used in the following [Example 4] and [Example 5].

After accelerated aging treatment of the coated titanium disk, Contact angle  Measurement experiment

A contact angle was measured after accelerated aging of a titanium disk coated with a mixed solution of a pH buffer substance and an organic amphoteric substance having a sulfone group.

The titanium disk prepared in [Example 3] was allowed to stand for 2, 4, 6 weeks and 12 weeks under the accelerated aging condition (about 55 ° C). 5 ml of distilled water was dropped on the disk to measure the contact angle, The contact angle was measured by close-up on the side. At this time, implants that did not remove contaminants were used as a negative control, and titanium disks that were pretreated to remove contaminants as a positive control but not coated with the mixed solution were used.

3, the contact angle of the negative control group was 107 °, and the contact angle of the positive control group and the experimental group was 0 °. On the other hand, in the positive control group, the contact angle was increased, And the organic amphiphile having a sulfone group, the contact angle was maintained at 0 degree even after accelerated aging, and the superhydrophilic property was maintained.

After accelerated aging treatment of the coated titanium disk, Attachment  Experiment

The cell adhesion capacity was measured on a titanium disk coated with a mixed solution of a pH buffer substance and an organic amphipatic substance having a sulfone group.

After the titanium disk prepared in [Example 3] was allowed to stand at an accelerated aging condition (about 55 ° C) for 2 weeks, MG63, an osteoblast cell line, was seeded at 1 × 10 ⁵ cells / The cells were incubated for 1 hour and quantified by cresyl violet assay. Implants that did not remove the contaminants were used as a negative control group, and implants that were pretreated to remove contaminants as a positive control group but not coated with the materials were used.

As can be seen from the results in FIG. 4, it was confirmed that the cell adhesion was increased in the positive control group as compared with the negative control group, and cell adhesion was similar to that in the positive control group in most of the experimental groups. In particular, it was confirmed that the organic amphiphilic substance having a sulfone group has excellent cell adhesion in a titanium disk using TES.

pH  With buffer substances Sulfone group  Having organic Amphibian  Coating Formation of Dental Implant Surface Using Mixed Solution (0.2M) of Substance

The surface of the dental implant was coated with a mixed solution of a pH buffer substance and an organic ampholytic substance having a sulfone group. Mechanical machined titanium implants were blasted with Al ₂ O ₃ powder with particle size of 1 mm or less for 1 ~ 60 seconds at blast pressure of 1 ~ 10 atm. Then, using acid treatment method using aqueous solution, macro- & micro -morphology. The surface of the dental titanium implant treated with acid was ultrasonically washed with ethanol and distilled water for 30 minutes, and then dried.

After the drying process, the implant was treated with plasma for 1 minute or ultraviolet for 5 minutes to remove the contamination source adsorbed and stabilized on the surface, and organic amphipathic substances (BES, HEPES, MOPS, TES) 0.2M aqueous solution. Dental implants coated in this manner were used in the following [Example 7] and [Example 8].

pH  Buffer substances and organic Amphibian  After a dental implant-accelerated aging treatment with a mixed solution of materials, blood affinity and blood proteins Attachment  Measure

After accelerated aging of dental implants coated with a mixture solution of pH buffer material and organic amphipatic material, blood affinity and adhesion capacity of blood proteins were measured.

The dental implants prepared by the method described in [Example 6] were allowed to stand for 1.5, 3, 4.5 and 7.5 weeks at accelerated aging conditions (about 75 ° C) After the implant was immersed in the aqueous solution of bovine serum albumin for about 1 mm, BSA adhered to the surface was confirmed by the BCA assay. Implants that did not remove contamination sources were used as a negative control group, and implants that were not coated with the mixed solution were used as a positive control group only after a pretreatment process to remove a contamination source.

As can be seen from the results of FIG. 5, despite the accelerated aging for 7.5 weeks, it can be confirmed that the implant coated with the mixed solution of the pH buffer material and the organic amphipat material having sulfone group retains or enhances the adherence of blood proteins. Especially, TES coated implants had the best ability to attach blood proteins.

The dental implant coated with the mixed solution of the pH buffer material and the organic amphoteric substance having the sulfone group prepared in [Example 6] was allowed to stand for 1.5, 3, 4.5 and 7.5 weeks under the accelerated aging condition (about 75 ° C) Then, to confirm the blood affinity, the coated implant was supported on the micropig blood by about 3 mm, and the blood wettability was confirmed by the height of the blood riding on the surface of the implant. At this time, as a control group, an implant which was subjected to a pretreatment process to remove contaminants but not coated with the material was used.

As can be seen from the photograph of FIG. 6, it can be visually confirmed that the implant coated with the mixed solution of the pH buffer material and the organic amphipat having the sulfone group has better blood wettability than that of the control group. Blood-friendly. Especially, blood affinity increased remarkably in the experimental group compared to the control group as the accelerated aging time increased.

After accelerated aging treatment of mixed solution coated dental implants, Bone interface strength  Measurement experiment

The dental implants coated with the mixed solution of the pH buffer material and the organic amphipathic substance having a sulfone group were subjected to accelerated aging treatment and the bone interface binding force was measured. The dental implant coated with the mixed solution prepared in [Example 6] was allowed to stand under accelerated aging condition (about 55 ° C) for 2 weeks. Then, the implant was placed in the micropig mandible to check the implant- After 16 days of bone formation period, removal torque was measured. Implants that did not remove contamination source were used as a negative control group, and implants that did not have a coating solution as a positive control group were pretreated to remove contaminants, but the mixed solution was not coated.

As shown in FIG. 7, it was confirmed that the torsion removing ability of the positive control group was increased by about 50% and the torsion removing ability of the test group was improved by about 20 to 40% compared with the negative control group, as compared with the negative control group. The improvement of the torsional removal force means that the implant - bone interfacial bonding strength is strengthened. In the experimental group, although the bone strength is slightly lower than that of the positive control group, the improvement of the bone interface strength is maintained at a similar level.

pH  With buffer substances Sulfone group  Having organic Amphibian  Coating experiment of dental implant surface using mixed solution of substance (0.05 ~ 1.68M)

 The surface of the dental implant was coated using a mixed solution (0.05 ~ 1M) of a pH buffer material and an organic amphiphile having a sulfone group.

The machined titanium implants were blasted with Al ₂ O ₃ powder with particle size of 1 mm or less for 1 ~ 60 seconds at blast pressure of 1 ~ 10 atm, and acid treatment was performed using mixed acid solution. The micro- and micro-morphology was formed on the surface of the implant. The acid-treated dental titanium implants were ultrasonically cleaned with ethanol and distilled water for 30 minutes, respectively, and dried.

(BES, HEPES, TES) having 0.05 to 1.68 M of sulfone groups on the surface of the implant, and the surface of the implant was treated with a plasma for 1 minute or ultraviolet ray for 5 minutes to remove the contaminants adsorbed and stabilized on the surface. The dental implant coated with the mixed solution of the pH buffer material and the organic ampholytic substance having sulfone groups thus prepared was used in Example 10 as follows.

Accelerated aging of mixed solution coated dental implants After processing , Blood protein Attachment  Measurement experiment

The dental implants coated with the mixed solution of the pH buffer substance and the organic ampholytic substance having a sulfone group were subjected to accelerated aging treatment to measure the adherence of blood proteins. After dental implants prepared in [Example 9] were allowed to stand for 6 weeks under accelerated aging conditions (about 75 ° C), the implant was immersed in 5% BSA (bovine serum albumin) After 1 mm loading, BSA adhered to the surface was confirmed by BCA assay.

As can be seen from the results of FIGS. 8 to 10, in spite of accelerated aging for 6 weeks, the implant coated with the organic amphipathic substance (BES, HEPES, TES) having the pH buffer substance and the sulfone group, It was confirmed that the binding ability of blood proteins was excellent in all of the concentrations of 0.05 to 1.0 M, and in particular, when the concentration range was in the range of 0.1 to 0.5 M, the ability to adhere blood proteins remarkably increased.

It is to be understood that the invention is not limited to the specific embodiment and description thereof, and that various changes and modifications may be made without departing from the spirit of the invention as claimed in the appended claims. And such variations are within the scope of protection of the present invention.

Claims (15)

1. A dental implant of titanium or titanium alloy having a rough surface,
A coating layer of a mixed solution containing i) an organic pH buffering material and / or an inorganic pH buffering material and ii) an organic ampholytic material having a sulfone group is formed on the rough surface that has been pretreated so as to remove a contaminant,
Wherein the organic pH buffer material has a pKa of 8.0 or more and at least one selected from AMPD, ammonia, bicine, glycine, glycylglycine, tris, tricine and taurine,
And with the inorganic pH buffer substance is a hydroxyl group, NaOH, KOH, Ca (OH ) 2, Ba (OH) 2, Al (OH) 3 and Sr (OH) at least one selected from among _2,
The organic amphiphilic substance having a sulfone group contained in the mixed solution includes at least one of BES, HEPES, MOPS and TES,
Wherein the mixed solution contains 0.05 to 1.68 M of organic amphipathic substance and the pH buffer substance is contained in a range of 1 to 10 wt% of the mixed solution. delete delete delete delete delete delete A first step of preparing a dental implant made of titanium or titanium alloy;
A second step of roughing the surface of the dental implant;
A third step of pretreating the roughened surface of the dental implant to remove contaminants; And
A fourth step of forming a coating layer of a mixed solution on the surface of the pretreated coarse dental implant i) an organic pH buffering substance and / or an inorganic pH buffering substance and ii) an organic ampholytic substance having a sulfone group,
Wherein the organic pH buffer material has a pKa of 8.0 or more and at least one selected from AMPD, ammonia, bicine, glycine, glycylglycine, tris, tricine and taurine,
The inorganic pH buffer substance has a hydroxyl group, is NaOH, KOH, Ca (OH) 2, Ba (OH) 2, Al (OH) 3 and Sr (OH) at least one selected from among _2,
The organic amphiphilic substance having a sulfone group contained in the mixed solution includes at least one of BES, HEPES, MOPS, and TES,
In the fourth step, the mixed solution contains 0.05 to 1.68 M of the organic amphipathic substance, and the pH buffer material is contained in the range of 1 to 10 wt% of the mixed solution. For implant. delete delete delete delete delete delete 9. The method of claim 8,
Wherein the step of removing the contamination source in the third step comprises treating the surface of the roughly treated dental implant with at least one of ultraviolet rays, RFGD (radio-frequency glow discharge), oxygen and normal temperature plasma, Method for manufacturing a dental implant of hydrophilic type.

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